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Artificial cell-cell communication in yeast Saccharomyces cerevisiae using signaling elements from Arabidopsis thaliana

Abstract

The construction of synthetic cell-cell communication networks can improve our quantitative understanding of naturally occurring signaling pathways and enhance our capabilities to engineer coordinated cellular behavior in cell populations. Towards accomplishing these goals in eukaryotes, we developed and analyzed two artificial cell-cell communication systems in yeast. We integrated Arabidopsis thaliana signal synthesis and receptor components with yeast endogenous protein phosphorylation elements and new response promoters. In the first system, engineered yeast 'sender' cells synthesize the plant hormone cytokinin, which diffuses into the environment and activates a hybrid exogenous/endogenous phosphorylation signaling pathway in nearby engineered yeast 'receiver' cells. For the second system, the sender network was integrated into the receivers under positive-feedback regulation, resulting in population density–dependent gene expression (that is, quorum sensing). The combined experimental work and mathematical modeling of the systems presented here can benefit various biotechnology applications for yeast and higher level eukaryotes, including fermentation processes, biomaterial fabrication and tissue engineering.

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Figure 1: Engineered cytokinin-based sender-receiver communication in yeast.
Figure 2: Cytokinin receiver characterization.
Figure 3: Microscopy observations of sender-receiver communication.
Figure 4: Engineered yeast quorum sensing.

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Acknowledgements

We thank Y. Gerchman, D. Karig, S. Basu and S. Subramanian for helpful discussions. We also thank T. Kakimoto and S. Avery for the gift of yeast strain and plasmids and R. Kerstetter for A. thaliana genomic DNA extract. This work was supported by a Burroughs Wellcome Fund fellowship.

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Correspondence to Ron Weiss.

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Supplementary information

Supplementary Fig. 1

Simulated cytokinin receiver behavior. (PDF 74 kb)

Supplementary Fig. 2

Simulated quorum sensing behaviors. (PDF 80 kb)

Supplementary Table 1

Definitions. (PDF 42 kb)

Supplementary Table 2

Chemical Reactions. (PDF 536 kb)

Supplementary Table 3

Differential Equations. (PDF 19 kb)

Supplementary Table 4

Kinetic Constants (units in μM and minute). (PDF 80 kb)

Supplementary Table 5

Plasmids used in this work. (PDF 45 kb)

Supplementary Table 6

Yeast strains used in this study. (PDF 32 kb)

Supplementary Note (PDF 85 kb)

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Chen, MT., Weiss, R. Artificial cell-cell communication in yeast Saccharomyces cerevisiae using signaling elements from Arabidopsis thaliana. Nat Biotechnol 23, 1551–1555 (2005). https://doi.org/10.1038/nbt1162

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